Adult outcomes of clinically relevant genomic disorders: A systematic review and meta-analysis

Genomic disorders comprise a major source of human disease with survival into adulthood for most individuals, but data on adult outcomes are limited.

We conducted a formal search to identify studies of 14 clinically relevant, molecularly confirmed deletion syndromes with ≥5 adults reporting on prevalence of cardiovascular risk and other outcomes. Outcomes were pooled across deletion syndromes and by syndrome, using random-effects models.

Of 1352 studies screened, 53 reported on nonoverlapping samples of 13 deletion syndromes. Estimated pooled prevalences, at age <30-40 for most, included 47% (95% CI 33-57%; n = 2076) for obesity, and for 10 deletion syndromes: diabetes 24% (95% CI 17-33%; n = 1739), hypertension 36% (95% CI 28-33%; n = 1314), and dyslipidemia 29% (95% CI 22-36%; n = 1127). High heterogeneity for each outcome was partly explained by a significant subgroup effect of individual syndrome. The few available mortality studies indicated premature mortality.

Pooled results suggest that, although there may be elevated prevalence of adult cardiovascular risk conditions, high heterogeneity indicates caution when considering rare deletion syndromes collectively. The paucity of data extending into later adulthood and using age-matched control comparisons supports the need for prospective studies of large, well-phenotyped cohorts to inform adult penetrance of treatable medical diseases in this emerging group of young adults.